Estimating Bidirectional Transitions and Identifying Predictors of Mild Cognitive Impairment

Abstract

Background and Objectives:Various resources exist for treating mild cognitive impairment (MCI) or dementia separately as terminal events or for focusing solely on a one-way path from MCI to dementia without taking into account heterogeneous transitions. Little is known about the trajectory of reversion from MCI to normal cognition (NC) or near-NC and patterns of post-reversion, which refers to cognitive trajectories of patients who have reversed from MCI to NC. Our objectives were to: 1) quantitatively predict bidirectional transitions of MCI (reversion and progression), 2) explore patterns of future cognitive trajectories for post-reversion, and 3) estimate the effects of demographic characteristics, apolipoprotein E (APOE), cognition, daily activity ability, depression and neuropsychiatric symptoms on transition probabilities.Methods:We constructed a retrospective cohort by reviewing patients with an MCI diagnosis at study entry and at least two follow-up visits between June 2005 and February 2021. Defining NC or near-NC and MCI as transient states and dementia as an absorbing state, we used continuous-time multi-state Markov models to estimate instantaneous transition intensity between states, transition probabilities from one state to another at any given time during follow-up, and hazard ratios of reversion-related variables.Results:Among 24,220 observations from 6,651 participants, there were 2,729 transitions to dementia and 1,785 reversions. As for post-reversion, there were 630 and 73 transitions of progression to MCI and dementia, respectively. The transition intensity of progression to MCI for post-reversion was 0.317 (2.48-fold greater than that for MCI progression or reversion). For post-reversion participants, the probability of progressing to dementia increased by 2% yearly. Participants who progressed to MCI were likely to reverse again (probability of 40% over 15 years). Age, independence level, APOE, cognition, daily activity ability, depression and neuropsychiatric symptoms were significant predictors of bidirectional transitions.Discussion:The nature of bidirectional transitions cannot be ignored in multi-dimensional MCI research. We found that post-reversion participants remained at an increased risk of progression to MCI or dementia over the longer term and experienced recurrent reversions. Our findings may serve as a valuable reference for future research and enable healthcare professionals to better develop proactive management plans and targeted interventions.

Motoric Cognitive Risk syndrome trajectories and incident dementia over 10 years

“…As MCI and MCR are both predementia syndromes sharing similar operational constructs, it is no surprise that individuals with MCR follow similar trajectories to those reported in the MCI literature [38,39]. A recent study of the bidirectional transitions of MCI (reversion and progression) in 6651 participants used a multistate modelling approach to estimate instantaneous transition intensity between the states and transition probabilities from one state to another at any given time during follow-up [39]. The authors found that post-reversion participants remained at an increased risk of progression to MCI or dementia over the longer term and experience recurrent reversions [39].…”

“…However, Mild Cognitive Impairment (MCI) is a predementia syndrome that has been studied more and over a longer period, including analyses of MCI trajectories [38]. As MCI and MCR are both predementia syndromes sharing similar operational constructs, it is no surprise that individuals with MCR follow similar trajectories to those reported in the MCI literature [38,39]. A recent study of the bidirectional transitions of MCI (reversion and progression) in 6651 participants used a multistate modelling approach to estimate instantaneous transition intensity between the states and transition probabilities from one state to another at any given time during follow-up [39].…”

“…A recent study of the bidirectional transitions of MCI (reversion and progression) in 6651 participants used a multistate modelling approach to estimate instantaneous transition intensity between the states and transition probabilities from one state to another at any given time during follow-up [39]. The authors found that post-reversion participants remained at an increased risk of progression to MCI or dementia over the longer term and experience recurrent reversions [39]. If the LBC1936 were a larger dataset, we would have liked to use multistate modelling approaches in our study to analyse if the same were true of our data.…”

Association between Life’s Essential 8 and cognitive function: insights from NHANES 2011–2014

“…Cognitive impairment can be categorized into several stages, from mild cognitive impairment (MCI) which is a transitional state between normal cognition and dementia to full-blown dementia (most commonly Alzheimer’s disease) ( Gaugler et al, 2022 ). The literature describes that about 20% of patients with MCI will develop dementia over time ( Qin et al, 2023 ). The number one cause of dementia is Alzheimer’s disease (AD) which is one of the costliest and a serious burden on society.…”

Neutrophil-Mediated Progression of Mild Cognitive Impairment to Dementia

“…The MCI can progress and lead to severe cognitive dysfunction in the aged brain. Approximately 20% of patients with MCI progressed to further cognitive deficits and dementia over time [8]. During the transition from MCI to dementia, the main causes and risk factors have been identified as non-modifiable factors, such as aging and genetic characteristics, and modifiable factors, such as physiological conditions due to degenerative disease and clinical characteristics [9].…”